Chromosome condensation during the mitosis is critical for proper bi-oriented chromosome separation (Hirano 2012; Thadani et al. 2012). The production of this mitosis-specific chromosome structure depends mainly on three multi-protein complexes: two condensin complexes and one cohesion complex (Wood et al. 2010). Each condensin complex is composed of two ATPase subunit heterodimers (structural maintenance of chromosomes (SMC) 2 & 4) and three non-SMC regulatory subunits (Wood et al. 2010; Hirano 2012). A unique set of three non-SMC regulatory components defines each condensin complex, NCAP-D2, NCAP-G, and NCAP-H are parts of condensin complex I, and NCAP-D3, NCAP-G2, and NCAP-H2 are components of condensin complex II (Wood et al. 2010; Green et al. 2012; Hirano 2012). NCAPG and NCAPD2 in condensin I, and NCAPG2 and NCAPD3 in condensin II are HEAT-repeat-containing regulatory subunits (Neuwald and Hirano 2000). Condensin complex I, which has a conserved structure in yeast and eukaryotes, is considered a canonical condensin complex for the condensation of eukaryotic chromosomes (Hirano 2012). Condensin complex II regulates not only chromosome condensation, but also diverse cellular functions, including chromosome segregation, DNA repair, sister chromatid resolution, gene expression regulation, and histone modulation (Hagstrom et al. 2002; Stear and Roth 2002; Ono et al. 2004; Smith et al. 2004; Xu et al. 2006; Wood et al. 2008; Csankovszki et al. 2009; Samoshkin et al. 2009; Liu et al. 2010; Floyd et al. 2013; Ono et al. 2013). Interestingly, homozygous mutants of all nematode condensin complex II components show nuclei of abnormal sizes or uneven distribution (Csankovszki et al. 2009). In human cells, the depletion of any components of condensin complex II also results in defects in chromosome alignment or segregation (Ono et al. 2004). Besides, the manner of regulation of chromosome segregation by each condensin component is dissimilar. While NCAPD3 depletion has a major effect on centrosome separation, NCAPG2 depletion appears more frequently as misaligned chromosomes in the metaphase plate (Ono et al. 2004). Recent studies have begun to address how each condensin components control regulatory function for the mitosis progress. For chromosome segregation in particular, recent reports have shown that NCAPD3 contributes to PLK1 loading in the chromosome arm. However, the detailed mechanical feature of each condensin complex II component regulating chromosome segregation is not known. Particularly, condensin complex II localized in kinetochore relative to condensin complex I (Hirota et al. 2004), the function of condensin complex II component in kinetochore for chromosome segregation is remained to dissolve.
The first step of chromosome segregation is the microtubule attachment to the kinetochore on the chromosome (Foley and Kapoor 2013). The kinetochore is the protein complex assembly that corresponds to the centromere of the chromosome where sister chromatids are linked (Foley and Kapoor 2013). The microtubule-kinetochore interactions require precise control to achieve the correct bi-oriented interaction. The early event of microtubule attachment to the kinetochore prior to the stabilization of interactions is governed by Polo-like kinase 1 (PLK1) (Barr et al. 2004; Lens et al. 2010; Carmena et al. 2012; Liu et al. 2012a; Foley and Kapoor 2013). PLK1 localizes diversely during mitosis according to the microtubule movement, from the centrosome to the kinetochore and then to the midbody (Lee et al. 1998; Barr et al. 2004; Lens et al. 2010). PLK1 localizes in the kinetochore until chromosome alignment is completed in the metaphase plate (Lens et al. 2010). When each kinetochore is not occupied properly by a microtubule, kinetochore-localized PLK1 phosphorylates BubR1, awaiting the onset of anaphase (Lampson and Kapoor 2005; Elowe et al. 2007; Matsumura et al. 2007; Liu et al. 2012a; Suijkerbuijk et al. 2012). Although it has been reported that some proteins in the kinetochore are responsible for PLK1 localization to the kinetochore, further research is needed to determine which substrate contributes to microtubule-dependent temporal and spatial rearrangements at the centromere to achieve microtubule binding (Foley and Kapoor 2013).
Here, we investigated the function of NCAPG2 in chromosome segregation during mitosis using C. elegans, a nematode model, and a human cell line. Our results demonstrate that NCAPG2 contributes to chromosome segregation by microtubule-kinetochore attachment regulation mediating PLK1 localization at the kinetochore. This function of NCAPG2 is conserved in both nematodes and mammals and is essential for achieving chromosome integrity in cell division.